tbuckley/cabot-search huggingface dataset:
NRG Oncology/RTOG1205: A Randomized Phase II Trial of Concurrent Bevacizumab and Reirradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma
Authors: Christina I. Tsien, Stephanie L. Pugh, Adam P. Dicker, Jeffrey J. Raizer, Martha M. Matuszak, Enrico C. Lallana, Jiayi Huang, Ozer Algan, Nimisha Deb, Lorraine Portelance, John L. Villano, John T. Hamm, Kevin S. Oh, Arif N. Ali, Michelle M. Kim, Scott M. Lindhorst, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2022)

PURPOSE To assess whether reirradiation (re-RT) and concurrent bevacizumab (BEV) improve overall survival (OS) and/or progression-free survival (PFS), compared with BEV alone in recurrent glioblastoma (GBM). The primary objective was OS, and secondary objectives included PFS, response rate, and treatment adverse events (AEs) including delayed CNS toxicities. METHODS NRG Oncology/RTOG1205 is a prospective, phase II, randomized trial of re-RT and BEV versus BEV alone. Stratification factors included age, resection, and Karnofsky performance status (KPS). Patients with recurrent GBM with imaging evidence of tumor progression ≥ 6 months from completion of prior chemo-RT were eligible. Patients were randomly assigned 1:1 to re-RT, 35 Gy in 10 fractions, with concurrent BEV IV 10 mg/kg once in every 2 weeks or BEV alone until progression. RESULTS From December 2012 to April 2016, 182 patients were randomly assigned, of whom 170 were eligible. Patient characteristics were well balanced between arms. The median follow-up for censored patients was 12.8 months. There was no improvement in OS for BEV + RT, hazard ratio, 0.98; 80% CI, 0.79 to 1.23; P = .46; the median survival time was 10.1 versus 9.7 months for BEV + RT versus BEV alone. The median PFS for BEV + RT was 7.1 versus 3.8 months for BEV, hazard ratio, 0.73; 95% CI, 0.53 to 1.0; P = .05. The 6-month PFS rate improved from 29.1% (95% CI, 19.1 to 39.1) for BEV to 54.3% (95% CI, 43.5 to 65.1) for BEV + RT, P = .001. Treatment was well tolerated. There were a 5% rate of acute grade 3+ treatment-related AEs and no delayed high-grade AEs. Most patients died of recurrent GBM. CONCLUSION To our knowledge, NRG Oncology/RTOG1205 is the first prospective, randomized multi-institutional study to evaluate the safety and efficacy of re-RT in recurrent GBM using modern RT techniques. Overall, re-RT was shown to be safe and well tolerated. BEV + RT demonstrated a clinically meaningful improvement in PFS, specifically the 6-month PFS rate but no difference in OS.
Fluid-Structure Interaction Within Models of Patient-Specific Arteries: Computational Simulations and Experimental Validations
Authors: Sabrina Schoenborn, Selene Pirola, Maria A. Woodruff, Mark C. Allenby
Journal: IEEE Reviews in Biomedical Engineering (2022)

Cardiovascular disease (CVD) is the leading cause of mortality worldwide and its incidence is rising due to an aging population. The development and progression of CVD is directly linked to adverse vascular hemodynamics and biomechanics, whose in-vivo measurement remains challenging but can be simulated numerically and experimentally. The ability to evaluate these parameters in patient-specific CVD cases is crucial to better predict future disease progression, risk of adverse events, and treatment efficacy. While significant progress has been made toward patient-specific hemodynamic simulations, blood vessels are often assumed to be rigid, which does not consider the compliant mechanical properties of vessels whose malfunction is implicated in disease. In an effort to simulate the biomechanics of flexible vessels, fluid-structure interaction (FSI) simulations have emerged as promising tools for the characterization of hemodynamics within patient-specific cardiovascular anatomies. Since FSI simulations combine the blood's fluid domain with the arterial structural domain, they pose novel challenges for their experimental validation. This paper reviews the scientific work related to FSI simulations for patient-specific arterial geometries and the current standard of FSI model validation including the use of compliant arterial phantoms, which offer novel potential for the experimental validation of FSI results.
Geographic Distribution and Workforce Diversity of Dermatology Physician Assistants—Reply
Authors: Justin D. Arnold, Andrzej Kozikowski
Journal: JAMA Dermatology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Gene Expression Profiling Identifies Two Chordoma Subtypes Associated with Distinct Molecular Mechanisms and Clinical Outcomes
Authors: Jiwei Bai, Jianxin Shi, Yazhuo Zhang, Chuzhong Li, Yujia Xiong, Hela Koka, Difei Wang, Tongwu Zhang, Lei Song, Wen Luo, Bin Zhu, Belynda Hicks, Amy Hutchinson, Erin Kirk, Melissa A. Troester, Mingxuan Li, Yutao Shen, Tianshun Ma, Junmei Wang, Xing Liu, Shuai Wang, Songbai Gui, Mary L. McMaster, Stephen J. Chanock, Dilys M. Parry, Alisa M. Goldstein, Xiaohong R. Yang
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Chordoma is a rare bone tumor with a high recurrence rate and limited treatment options. The aim of this study was to identify molecular subtypes of chordoma that may improve clinical management. Experimental Design: We conducted RNA sequencing in 48 tumors from patients with Chinese skull-base chordoma and identified two major molecular subtypes. We then replicated the classification using a NanoString panel in 48 patients with chordoma from North America. Results: Tumors in one subtype were more likely to have somatic mutations and reduced expression in chromatin remodeling genes, such as PBRM1 and SETD2, whereas the other subtype was characterized by the upregulation of genes in epithelial–mesenchymal transition and Sonic Hedgehog pathways. IHC staining of top differentially expressed genes between the two subtypes in 312 patients with Chinese chordoma with long-term follow-up data showed that the expression of some markers such as PTCH1 was significantly associated with survival outcomes. Conclusions: Our findings may improve the understanding of subtype-specific tumorigenesis of chordoma and inform clinical prognostication and targeted options.
Compensatory Genetic and Transcriptional Cytonuclear Coordination in Allopolyploid Lager Yeast (<i>Saccharomyces pastorianus</i>)
Authors: Keren Zhang, Juzuo Li, Guo Li, Yue Zhao, Yuefan Dong, Ying Zhang, Wenqing Sun, Junsheng Wang, Jinyang Yao, Yiqiao Ma, Hongyan Wang, Zhibin Zhang, Tianya Wang, Kun Xie, Jonathan F Wendel, Bao Liu, Lei Gong
Journal: Molecular Biology and Evolution (2022)

Abstract Cytonuclear coordination between biparental-nuclear genomes and uniparental-cytoplasmic organellar genomes in plants is often resolved by genetic and transcriptional cytonuclear responses. Whether this mechanism also acts in allopolyploid members of other kingdoms is not clear. Additionally, cytonuclear coordination of interleaved allopolyploid cells/individuals within the same population is underexplored. The yeast Saccharomyces pastorianus provides the opportunity to explore cytonuclear coevolution during different growth stages and from novel dimensions. Using S. pastorianus cells from multiple growth stages in the same environment, we show that nuclear mitochondria-targeted genes have undergone both asymmetric gene conversion and growth stage-specific biased expression favoring genes from the mitochondrial genome donor (Saccharomyces eubayanus). Our results suggest that cytonuclear coordination in allopolyploid lager yeast species entails an orchestrated and compensatory genetic and transcriptional evolutionary regulatory shift. The common as well as unique properties of cytonuclear coordination underlying allopolyploidy between unicellular yeasts and higher plants offers novel insights into mechanisms of cytonuclear evolution associated with allopolyploid speciation.
Systemic Interventions for Treatment of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis
Authors: Megan H. Noe, Robert G. Micheletti
Journal: JAMA Dermatology (2022)

What are the effects of systemic therapies for Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)?There is limited high-quality evidence to support the use of systemic immunomodulatory therapies to decrease mortality rates in SJS/TEN.
Gender-Affirming Care of Transgender and Gender-Diverse Youth: Current Concepts
Authors: Janet Y. Lee, Stephen M. Rosenthal
Journal: Annual Review of Medicine (2022)

Increasing numbers of transgender and gender-diverse (TGD) youth, from early puberty through late adolescence, are seeking medical services to bring their physical sex characteristics into alignment with their gender identity-their inner sense of self as male or female or elsewhere on the gender spectrum. Numerous studies, primarily of short- and medium-term duration (up to 6 years), demonstrate the clearly beneficial-even lifesaving-mental health impact of gender-affirming medical care in TGD youth. However, there are significant gaps in knowledge and challenges to such care. Long-term safety and efficacy studies are needed to optimize medical care for TGD youth.
Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage
Authors: Maria Ercu, Michael B. Mücke, Tamara Pallien, Lajos Markó, Anastasiia Sholokh, Carolin Schächterle, Atakan Aydin, Alexa Kidd, Stephan Walter, Yasmin Esmati, Brandon J. McMurray, Daniella F. Lato, Daniele Yumi Sunaga-Franze, Philip H. Dierks, Barbara Isabel Montesinos Flores, Ryan Walker-Gray, Maolian Gong, Claudia Merticariu, Kerstin Zühlke, Michael Russwurm, Tiannan Liu, Theda U.P. Batolomaeus, Sabine Pautz, Stefanie Schelenz, Martin Taube, Hanna Napieczynska, Arnd Heuser, Jenny Eichhorst, Martin Lehmann, Duncan C. Miller, Sebastian Diecke, Fatimunnisa Qadri, Elena Popova, Reika Langanki, Matthew A. Movsesian, Friedrich W. Herberg, Sofia K. Forslund, Dominik N. Müller, Tatiana Borodina, Philipp G. Maass, Sylvia Bähring, Norbert Hübner, Michael Bader, Enno Klussmann
Journal: Circulation (2022)

Phosphodiesterase 3A (
Evaluation of the Association of Platelet Count, Mean Platelet Volume, and Platelet Transfusion With Intraventricular Hemorrhage and Death Among Preterm Infants
Authors: Chong Chen, Sicheng Wu, Jia Chen, Jinghui Wu, Yabo Mei, Tao Han, Changshuan Yang, Xilin Ouyang, May Chun Mei Wong, Zhichun Feng
Journal: JAMA Network Open (2022)

Platelet transfusion is commonly performed in infants to correct severe thrombocytopenia or prevent bleeding. Exploring the associations of platelet transfusion, platelet count (PC), and mean platelet volume (MPV) with intraventricular hemorrhage (IVH) and in-hospital mortality in preterm infants can provide evidence for the establishment of future practices.To evaluate the associations of platelet transfusion, PC, and MPV with IVH and in-hospital mortality and to explore whether platelet transfusion-associated IVH and mortality risks vary with PC and MPV levels at the time of transfusion.This retrospective cohort study included preterm infants who were transferred to the neonatal intensive care unit on their day of birth and received ventilation during their hospital stay. The study was conducted at a neonatal intensive care unit referral center in Beijing, China, between May 2016 and October 2017. Data were retrieved and analyzed from December 2020 to January 2022.Platelet transfusion, PC, and MPV.Any grade IVH, severe IVH (grade 3 or 4), and in-hospital mortality.Among the 1221 preterm infants (731 [59.9%] male; median [IQR] gestational age, 31.0 [29.0-33.0] weeks), 94 (7.7%) received 166 platelet transfusions. After adjustment for potential confounders, platelet transfusion was significantly associated with mortality (hazard ratio [HR], 1.48; 95% CI, 1.13-1.93; P = .004). A decreased PC was significantly associated with any grade IVH (HR per 50 × 103/μL, 1.13; 95% CI, 1.05-1.22; P = .001), severe IVH (HR per 50 × 103/μL, 1.16; 95% CI, 1.02-1.32; P = .02), and mortality (HR per 50 × 103/μL, 1.74; 95% CI, 1.48-2.03; P < .001). A higher MPV was associated with a lower risk of mortality (HR, 0.83; 95% CI, 0.69-0.98; P = .03). The platelet transfusion-associated risks for both IVH and mortality increased when transfusion was performed in infants with a higher PC level (eg, PC of 25 × 103/μL: HR, 1.20; 95% CI, 0.89-1.62; PC of 100 × 103/μL: HR, 1.40; 95% CI, 1.08-1.82). The platelet transfusion-associated risks of IVH and mortality varied with MPV level at the time of transfusion.In preterm infants, platelet transfusion, PC, and MPV were associated with mortality, and PC was also associated with any grade IVH and severe IVH. The findings suggest that a lower platelet transfusion threshold is preferred; however, the risk of a decreased PC should not be ignored.
Intrinsic Molecular Subtypes of Metastatic Castration-Resistant Prostate Cancer
Authors: Eric Feng, Nicholas R. Rydzewski, Meng Zhang, Arian Lundberg, Matthew Bootsma, Kyle T. Helzer, Joshua M. Lang, Rahul Aggarwal, Eric J. Small, David A. Quigley, Martin Sjöström, Shuang G. Zhao
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Although numerous biology-driven subtypes have been described previously in metastatic castration-resistant prostate cancer (mCRPC), unsupervised molecular subtyping based on gene expression has been less studied, especially using large cohorts. Thus, we sought to identify the intrinsic molecular subtypes of mCRPC and assess molecular and clinical correlates in the largest combined cohort of mCRPC samples with gene expression data available to date. Experimental Design: We combined and batch-effect corrected gene expression data from four mCRPC cohorts from the Fred Hutchinson Cancer Research Center (N = 157), a small-cell neuroendocrine (NE) prostate cancer (SCNC)–enriched cohort from Weill Cornell Medicine (N = 49), and cohorts from the Stand Up 2 Cancer/Prostate Cancer Foundation East Coast Dream Team (N = 266) and the West Coast Dream Team (N = 162). Results: Hierarchical clustering of RNA-sequencing data from these 634 mCRPC samples identified two distinct adenocarcinoma subtypes, one of which (adeno-immune) was characterized by higher gene expression of immune pathways, higher CIBERSORTx immune scores, diminished ASI benefit, and non–lymph node metastasis tropism compared with an adeno-classic subtype. We also identified two distinct subtypes with enrichment for an NE phenotype, including an NE-liver subgroup characterized by liver metastasis tropism, PTEN loss, and APC and SPOP mutations compared with an NE-classic subgroup. Conclusions: Our results emphasize the heterogeneity of mCRPC beyond currently accepted molecular phenotypes, and suggest that future studies should consider incorporating transcriptome-wide profiling to better understand how these differences impact treatment responses and outcomes.
Current Status of National Institutes of Health Research Funding for Women Surgeon-Scientists
Authors: Areeba Saif, Lindsay A. Demblowski, Andrew M. Blakely, Martha A. Zeiger
Journal: JAMA Surgery (2022)

Women have made substantial advancements in academic surgery, but research funding disparities continue to hamper their progress, and current literature on the status of National Institutes of Health (NIH) funding awarded to women surgeon-scientists appears to be conflicting.To examine gender-based differences in NIH funding awarded to surgeon-scientists by comparing total grant amounts awarded and the distribution of grants by gender and research type.This cross-sectional study was performed using a previously created database of NIH-funded surgeons from 2010 to 2020. Active physician data from the Association of American Medical Colleges were used to calculate total surgeon populations. This study was performed at the NIH using the NIH internal data platform, iSearch Grants. A total of 715 men and women surgeon-scientists funded by the NIH in 2010 and 1031 funded in 2020 were included in the analysis.The main outcome was the number of women among the total number of surgeons who received NIH grants and the total grant amounts awarded to them. Bivariate χ2 analyses were performed using population totals and substantiated by z tests of population proportions.This study included 715 physicians (n = 579 men [81.0%]) in 2010 and 1031 physicians (n = 769 men [74.6%]) in 2020. In 2020, women comprised 27.4% of the surgical workforce and 25.4% of surgeons with research funding in the US, but they received only 21.7% of total NIH research funding awarded to all surgeons. The number of funded women surgeon-scientists, however, significantly increased from 2010 to 2020 (262 [25.4%] in 2020 vs 136 [19.0%] in 2010; P < .001) as did their funding ($189.7 million [21.7%] in 2020 vs $75.9 million [12.3%] in 2010; P < .001). Furthermore, the proportion of US women surgeons overall with NIH funding significantly increased in 2020 vs 2010 (0.7% vs 0.5%; P < .001). Basic science, clinical outcomes, and clinical trial R01 grants also increased among women surgeon-scientists. Women and men K grant holders had a similar mean (SD) number of R01 application attempts before success (2.7 [3.01] vs 2.3 [3.15]; P = .60) and similar K-to-R award conversion rates (23.5% vs 26.7%; P = .55).This cross-sectional study found an increasing number of women surgeon-scientists receiving NIH funding in 2020 vs 2010 as well as increases in the median grant amounts awarded. Although these results are promising, a discrepancy remains in the proportion of women in the surgical workforce compared with those funded by the NIH and the total grant amounts awarded to them.
The FDG Pattern of Autonomously Functioning Thyroid Nodules Correlates With Thyroid-Stimulating Hormone and Histopathology
Authors: Arnoldo Piccardo, Francesco Fiz, Gianluca Bottoni, Michela Massollo, Matteo Puntoni, Ugo Catrambone, Luca Foppiani, Francesco Bertagna, Domenico Albano, Pierpaolo Trimboli
Journal: Clinical Nuclear Medicine (2022)

Whereas the 18 F-FDG PET/CT pattern of malignant thyroid neoplasia is known, the glucose uptake of autonomously functioning thyroid nodules (AFTNs) has not been fully investigated. We aimed to analyze the FDG uptake of AFTNs and its correlation with clinical, laboratory, ultrasonography, and histological features.We retrospectively analyzed the records of all AFTN patients from 2 centers, in which an 18 F-FDG PET/CT, thyroid function tests, and neck ultrasound were available within a 3-month window from the thyroid scintigraphy. Forty-five patients (35 female patients; median age, 65 years) were retrospectively included. The presence of FDG uptake was compared with the laboratory data and, whenever available, the histology.Over a 36-month follow-up, 20 patients underwent surgery; 4 cancers, 10 follicular adenomas, and 6 follicular hyperplasias were found. Twenty-two AFTNs (48.9%) were FDG-positive, whereas the remaining 23 (51.1%) were not. Thyroid-stimulating hormone (TSH) was significantly lower in FDG-positive AFTNs than in negative ones (0.055 [0.02-0.42] vs 0.65 [0.2-0.96] mIU/L, P = 0.0018). On multivariate analysis, only TSH was independently associated with FDG uptake ( P = 0.008). On receiver operating characteristic curve analysis, TSH <0.08 mIU/L indicated FDG-positive AFTNs, with 64% sensitivity, 87% specificity, 4.88 positive likelihood ratio, and 0.42 negative likelihood ratio. In histologically proven benign lesions, TSH was significantly lower in follicular adenomas than in follicular hyperplasias ( P < 0.001). Patients with cancer had TSH in the low-normal range.Autonomously functioning thyroid nodules show heterogeneous uptake FDG pattern, which depends on histopathology and thyroid function. Particularly, follicular adenomas tend to display increased glucose uptake and suppressed TSH.
Maternal hypertensive disorder of pregnancy and mortality in offspring from birth to young adulthood: national population based cohort study
Authors: Chen Huang, Kecheng Wei, Priscilla Ming Yi Lee, Guoyou Qin, Yongfu Yu, Jiong Li
Journal: BMJ (2022)

To examine the association of maternal hypertensive disorder of pregnancy (HDP) with overall and cause specific mortality in offspring from birth to young adulthood.Nationwide population based cohort study.Danish national health registers.All 2 437 718 individuals live born in Denmark, 1978-2018, with follow-up from date of birth until date of death, emigration, or 31 December 2018, whichever came first.The primary outcome was all cause mortality. Secondary outcomes were 13 specific causes of death in offspring from birth to young adulthood (age 41 years). Cox regression was used to assess the association, taking into consideration several potential confounders. The role of timing of onset and severity of pre-eclampsia, maternal history of diabetes, and maternal education were also studied.102 095 mothers had HDP: 67 683 with pre-eclampsia, 679 with eclampsia, and 33 733 with hypertension. During follow-up to 41 years (median 19.4 (interquartile range 9.7-28.7) years), deaths occurred in 781 (58.94 per 100 000 person years) offspring born to mothers with pre-eclampsia, 17 (133.73 per 100 000 person years) born to mothers with eclampsia, 223 (44.38 per 100 000 person years) born to mothers with hypertension, and 19 119 (41.99 per 100 000 person years) born to mothers with no HDP. The difference in cumulative incidence in overall mortality between cohorts exposed and unexposed to maternal HDP was 0.37% (95% confidence interval 0.11% to 0.64%), and the population attributable fraction for maternal HDP was estimated as 1.09% (95% confidence interval 0.77% to 1.41%). Maternal HDP was associated with a 26% (hazard ratio 1.26, 95% confidence interval 1.18 to 1.34) higher risk of all cause mortality in offspring. The corresponding estimates for maternal pre-eclampsia, eclampsia, and hypertension were 1.29 (1.20 to 1.38), 2.88 (1.79 to 4.63), and 1.12 (0.98 to 1.28). Increased risks were also observed for several cause specific mortalities, such as deaths from conditions originating in the perinatal period (2.04, 1.81 to 2.30), cardiovascular diseases (1.52, 1.08 to 2.13), digestive system diseases (2.09, 1.27 to 3.43), and endocrine, nutritional, and metabolic diseases (1.56, 1.08 to 2.27). The increased risks were more pronounced among offspring of mothers with early onset and severe pre-eclampsia (6.06, 5.35 to 6.86) or with both HDP and diabetes history (1.57, 1.16 to 2.14) or HDP and low education level (1.49, 1.34 to 1.66).Maternal HDP, particularly eclampsia and severe pre-eclampsia, is associated with increased risks of overall mortality and various cause specific mortalities in offspring from birth to young adulthood.